A de novo mosaic mutation of PHEX in a boy with hypophosphatemic rickets

X-linked dominant hypophosphatemic rickets (xlhr), is characterized mainly by renal phosphate wasting with hypophosphatemia, short stature and abnormal bone mineralization. phex, located at xp22.1–p22.2, is the gene causing xlhr. we aim to characterize the pathogenesis of a chinese boy who is apparently ‘heterozygous’ in phex gene. direct sequencing showed two peaks: one was a wild-type ’g’ and the other was one base substitution to ‘a’, though the patient was a male. ta clone assay clearly showed each sequences and the ratios. the mutation effect was predicted via bioinformatics and validated by exon-trapping assay. real-time pcr was applied to determine the copy number of phex. ta clone assay showed the frequency of normal (g) to mutant allele (a) as 19:13. normal karyotype and real-time pcr results indicate the normal copy number of phex. this splice site mutation leads to 4 bp of exon 18 skipping out causing frame shift p.gly590glufs*28 that ends up with a loss of active site and zn2+-binding site of phex, which probably interfere with renal phosphate reabsorption and bone mineralization. in conclusion, mutation at conserved splice acceptor site resulted in aberrant splicing, ending up with a damaged protein product. this novel mutation is de novo in mosaic pattern that may be induced during early postzygotic period. taking mosaic somatic mutation of phex into consideration is strongly suggested in genetic counseling and etiology research for xlhr.